Immunological Implications of Pregnancy Flashcards
what can early pregnancy be defined as?
implantation and placentation
what is necessary for successful implantation?
localized inflammatory responses/ acute phase response
what are the acute phase cytokines?
IL-1, IL-8, IL-6, Il-12, TNF, IFN-gamma
what is the purpose of the acute phase cytokines?
they disrupt the mucin barrier of the endometrium and promote adhesion molecule expression
what immune cells are present in the early pregnancy stage?
decidual NKs, macrophages, neutrophils, and decidual dendritic cells
after we attach, we have to go through what stage?
the implantation stage
during the implantation stage, what acute phase cytokines would you expect to see a lot of?
IL-6 and IL-1
what is the role of macrophages during the implantation phase?
they help to sustain the corpus luteum and in the decidua they participate in spiral artery remodeling; they also still provide waste management of cellular debris from invasion of trophoblast
what type of macrophages are found pre-implantation?
MI macrophages- responsible for inflammation
what happens to the macrophages after implantation?
the ratio of M1 macrophages and M2 macrophages is equal
what are the roles of the dDCs during the implantation phase?
they are important for the maintenance of the dTregs, they secrete IL-15, and the promote a Th2 phenotype
what is the role of the dNK cells during implantation?
they directly surround the trophoblasts after implantation and support their development
what are the dNK cells critical for during the implantation phase?
spiral artery development
what type of receptors do the dNK cells have?
inhibitory receptors for HLA-C, E, and G
what do trophoblasts secrete and why?
they secrete cytokines and chemokines for the recruitment of immune cells for “support” and appropriate placentation
what immune cells do the trophoblasts secrete?
dNKcells, M2 macrophages, Treg cells
why are trophoblasts bringing immune cells into the are?
they are bringing them into the area to train them to become suppressor or tolerance cells
what does it mean when it is said that trophoblasts have a unique HLA expression?
it is very specific for the fetal/placental antigen presentation that is going to be doing that low level presentation to mom and periphery throughout gestation; it regulates fetal and placental antigen presentation to immune cells
how do the syncytiotrophoblasts provide protection from pathogens?
they express TLRs; that always express IFN-gamma, which provides antiviral resistance; they have a dense actin cytoskeleton network that helps physically resist invasion by bacteria/viruses
what do STs shed into the maternal circulation and decidua and why?
they shed a variety of extracellular vesicles- it is driving tolerance
what effect does a dramatic increase in the quantity of extracellular vesicles in the peripheral blood of pregnant females have?
pre-eclampsia, gestational diabetes, and pre-term birth
what chemokines/ cytokines do the extravillous trophoblasts secrete and why?
IL-15, CCL2, TGF-beta, IL-10, abd type I IFNs; for immune cell recruitment and regulation
what are the immune protective functions of EVTs with dNK cells?
they reduce the cytotoxicity of dNK cells while supporting their role in vascular remodeling (through IL-15 and HLA-G)
how do the EVTs support M2 differentiation?
IL-10
how do the EVTs support Treg differentiation?
TGF-beta
what cells are critical for spiral artery development during the implantation phase?
dNK cells
what do trophoblasts have that are sensing a variety of bacteria, virus, and DAMPS for protections?
TLRs
what do syncytiotrophoblasts have on their surface that help transport the immunoglobulins?
FcRn for IgG
what is the purpose of the IFN-lambda secreted by the syncytiotrophoblast?
it provides antiviral resistance for self and surrounding tissues
what is constitutively expressed on EVTs and why?
PD-1- it down regulates and inhibits T cell responses
what is a potential role of HLA-G during pregnancy?
maintenance of peripheral tolerance to the fetus
what have reduced levels of soluble HLA-G been associated with during pregnancy?
pregnancy complications such as preeclampsia
faulty expression of what cytokines can lead to developmental failure in multiple organ systems- neurological development?
IFN-gamma, IFN A/B, TNF-a, IL-6, IL-17, and IL-1B
what happens to the decidual NK cells during the tolerance/ fetal growth phase?
they become helper cells versus cytotoxic; they promote trophoblast invasion and angiogenesis
As pregnancy progresses, what do the decidual NK cells promote?
expanded Treg differentiation
how do the decidual NK cells promote expansion of the Treg differentiation?
IL-10, IDO, and TGF-beta
what do the decidual macrophages function as during the tolerance/fetal growth phase?
suppressor cells
how do the dMacrophages support the continued induction of Tregs in the decidua?
by secretion of IL-10
how do the dMacrophages support the dNK cells in the decidua?
by secretion of IL-15
what effect do dMacrophages have on antigen presentation?
they decrease antigen presentation to CD4/CD8 t effector cells through expression of HLA-G
what are the majority of dDCS during the first two trimesters of pregnancy?
the conventional myeloid DCs
what happens to the myeloid DCs in late pregnancy?
they decrease as the number of plasmacytoid DCs increased
what is a very large population of CD4+ T cells in the decidua?
Tregs
what two things play a major role in inducing Tregs in the decidua?
EVTs and dMacrophages
what do all subsets of Tregs in the decidua express?
CTLA-4
what is the effect of Tregs expressing CTLA-4?
during antigen presentation by APCs, CTLA-4 will bind to B7 on the APCs and induce anergy
what are the majority of non-treg lymphocytes in the decidua?
CD4+ Th2 cells
why do we have Th2 cells in the decidua?
they are specialized for anti parasite protection and protection against pathogens
what new cells do we see during the delivery phase?
Th17, T effector cells, neutrophils, and DAMPS and prostaglandins
